What coagulation factors constitute the intrinsic Xase (intrinsic factor X activator) complex?

Intrinsic Xase Complex Composition

The intrinsic Xase complex is composed of factors IXa, VIIIa, phospholipid, and Ca²⁺ (option B).

Understanding the Coagulation Cascade Components

The coagulation cascade is a complex process involving multiple factors that work together to form a fibrin clot. Within this cascade, there are two key enzymatic complexes that activate factor X:

1. Intrinsic Xase Complex (Intrinsic Factor X Activator):

   • Composed of activated factor IX (FIXa)
   • Activated factor VIII (FVIIIa) as cofactor
   • Phospholipid surface (typically provided by activated platelets)
   • Calcium ions (Ca²⁺) 1

2. Extrinsic Xase Complex (Extrinsic Factor X Activator):

   • Composed of activated factor VII (FVIIa)
   • Tissue Factor (TF)
   • Calcium ions (Ca²⁺) 2

Role of the Intrinsic Xase in Coagulation

The intrinsic Xase complex plays a critical role in the amplification phase of coagulation:

• It forms on phospholipid surfaces (typically activated platelets)
• FIXa serves as the enzyme component
• FVIIIa acts as a cofactor that dramatically enhances the catalytic efficiency
• This complex activates factor X approximately 200,000-fold more efficiently than FIXa alone 3
• The complex is essential for sustained thrombin generation 1

Molecular Interactions in the Intrinsic Xase

The assembly of the intrinsic Xase complex involves specific molecular interactions:

• FVIIIa binds to phospholipid surfaces through its C2 domain
• FIXa interacts with FVIIIa, which positions it optimally for factor X activation
• Calcium ions are essential for the proper conformation of both FIXa and FVIIIa
• The phospholipid surface provides the necessary platform for these interactions 4

Distinguishing from Other Complexes

It's important to differentiate the intrinsic Xase complex from other complexes in the coagulation cascade:

• Prothrombinase complex: Consists of factors Xa, Va, phospholipid, and Ca²⁺ (option D) - this complex converts prothrombin to thrombin 1
• Contact activation complex: Involves factors XIIa, XIa, and other contact system proteins (partially represented in option A)
• Extrinsic Xase complex: Consists of factor VIIa, tissue factor (TF), and Ca²⁺ (option C) 2

Clinical Significance

Understanding the composition of the intrinsic Xase complex is clinically relevant because:

• Deficiencies in factors VIII or IX result in hemophilia A and B respectively
• The intrinsic Xase complex is a target for anticoagulant therapies
• This complex is essential for the amplification of thrombin generation, which directly impacts morbidity and mortality in thrombotic and hemorrhagic disorders 5

The intrinsic Xase complex (factors IXa, VIIIa, phospholipid, and Ca²⁺) represents a critical node in the coagulation cascade where the intrinsic pathway contributes to sustained thrombin generation necessary for stable clot formation.